High throughput screening of ultrafiltration and diafiltration processing of monoclonal antibodies via the ambr (R) crossflow system

摘要

As the biopharmaceutical industry moves toward high concentration of monoclonal antibody drug substance, additional development is required early on when material is still limited. A key constraint is the availability of predictive high-throughput low-volume filtration screening systems for bioprocess development. This particularly impacts final stages such as ultrafiltration/diafiltration steps where traditional scale-down systems need hundreds of milliliters of material per run. Recently, the ambr (R) crossflow system has been commercialized by Sartorius Stedim Biotech (SSB) to meet this need. It enables parallel high throughput experimentation by only using a fraction of typical material requirements. Critical parameters for predictive filtration systems include loading, mean transmembrane pressure (Delta P over bar (TMP)), and crossflow rate (Q(F)). While axial pressure drop (Delta P-axial) across the cartridge is a function of these parameters, it plays a key role and similar values should result across scales. The ambr (R) crossflow system is first presented describing typical screening experiments. Its performance is then compared to a traditional pilot-scale tangential flow filtration (TFF) at defined conditions. The original ambr (R) crossflow (CF) cartridge underperformed resulting in similar to 20x lower Delta P-axial than the pilot-scale TFF flat-sheet cassette. With an objective to improve the scalability of the system, efforts were made to understand this scale difference. The ambr (R) CF cartridge was successfully modified by restricting the flow of the feed channel, and thus increasing its Delta P-axial. Additional studies across a range of loading (100-823 gm(-2)); Delta P over bar (TMP) (12-18 psi); and Q(F) (4-8 L/min/m(2)) were conducted in both scales. Comparable flux and aggregate levels were achieved.